This Phase 1 exploratory study assesses the safety and feasibility of repeated transcranial direct current stimulation (tDCS) in combination with intensive speech-language treatment (SLT) and collects preliminary data about its efficacy under different polarity conditions in individuals with chronic nonfluent aphasia. Facilitating brain plasticity with the direct application of stimulation to the cerebral cortex has been studied in animal models with promising results and subsequently applied to the rehabilitation of motor deficits after stroke. Application to language problems after stroke is only emerging, but results suggest a potential role for cortical stimulation as an adjuvant strategy in aphasia rehabilitation. Of the methods available, tDCS has the greatest potential for clinical use in view of its non-invasive application, ease of administration and relative low cost. However, there is insufficient data regarding safety when it is applied daily over a prolonged period of time (e.g. during several weeks of rehabilitation). Furthermore, the question of where best to apply the stimulation for individuals with aphasia has not been previously addressed i.e. anodal or cathodal to the lesioned left hemisphere or to the intact right hemisphere. Accordingly, the specific aims of this study are to assess the safety of 1 mA tDCS (anodal, cathodal, or sham stimulation) when applied for 13 minutes, 5 days a week for 6 weeks in combination with intensive SLT. In addition, the therapeutic efficacy and neurobiological change associated with each mode of stimulation are assessed and compared. Twelve individuals with severe or moderately-severe nonfluent aphasia are randomized to one of three groups: anodal tDCS to the left hemisphere;cathodal tDCS to the left hemisphere;or sham stimulation. Site of stimulation is determined from fMRI tasks of observation, imitation, oral reading, and word generation with activation in left premotor cortex in one of three intersection maps indicating site of stimulation. Treatment includes 1 mA tDCS (or sham stimulation) for 13 minutes simultaneously with speech-language therapy (SLT), followed by an additional 77 minutes of SLT for a total of 90 minutes of SLT. SLT is provided via computer and involves oral reading of sentences and conversational practice. The primary endpoint is safety, measured by the number of adverse events or evidence of cognitive or language decline. The primary therapeutic outcome measure is the change in the Western Aphasia Battery Aphasia Quotient from pretreatment to post-treatment, with secondary outcome measures including change scores on the Boston Naming Test, the Communicative Effectiveness Index, and discourse measures of informational content and rate. Neurobiological measures include change in total volume of activation for each hemisphere and for regions of interest including the lateral premotor area (including the pars opercularis of the inferior frontal gyrus). tDCS in combination with SLT may be safe and may lead to improved outcomes, with important implications for the costs and delivery of rehabilitation services for individuals with aphasia. PUBLIC HEALTH RELEVANCE: Aphasia is a common symptom of stroke that has enormous impact on the individual's day-to-day functional activities and emotional well-being. Transcranial direct current stimulation (tDCS) in combination with speech and language therapy may lead to improved outcomes and have important implications for the costs and delivery of rehabilitation services for individuals with aphasia. Optimizing language recovery and enhancing the quality of life of individuals with aphasia may facilitate their entry back into the community and the work force, thereby decreasing the financial costs to society.